Abstract
Live attenuated vaccines play a key role in the control of many human and animal pathogens. Their rational development is usually helped by identification of the reservoir of infection, the lymphoid subpopulations associated with protective immunity as well as the virulence genes involved in pathogen persistence. Here, we compared the course of Brucella melitensis infection in C57BL/6 mice infected via intraperitoneal (i.p.), intranasal (i.n.) and intradermal (i.d.) route and demonstrated that the route of infection strongly impacts all of these parameters. Following i.p. and i.n. infection, most infected cells observed in the spleen or lung were F4/80+ myeloid cells. In striking contrast, infected Ly6G+ neutrophils and CD140a+ fibroblasts were also observed in the skin after i.d. infection. The virB operon encoding for the type IV secretion system is considered essential to deflecting vacuolar trafficking in phagocytic cells and allows Brucella to multiply and persist. Unexpectedly, the ΔvirB Brucella strain, which does not persist in the lung after i.n. infection, persists longer in skin tissues than the wild strain after i.d. infection. While the CD4+ T cell-mediated Th1 response is indispensable to controlling the Brucella challenge in the i.p. model, it is dispensable for the control of Brucella in the i.d. and i.n. models. Similarly, B cells are indispensable in the i.p. and i.d. models but dispensable in the i.n. model. γδ+ T cells appear able to compensate for the absence of αβ+ T cells in the i.d. model but not in the other models. Taken together, our results demonstrate the crucial importance of the route of infection for the host pathogen relationship.
Highlights
Live attenuated vaccines (LAVs), composed of live pathogens that are made much less virulent than the pathogenic parental strains, are one of the most cost effective health tools in medical history [for review see [1,2,3]]
In order to determine the impact of the route of Brucella infection on the pattern of infected organs in mice, we administered 2 × 104 CFU of mCherry-Brucella melitensis via i.p., i.n. or i.d. route to wild-type C57BL/6 mice
Compared to LAVs, subunit vaccines (SUVs) offer several advantages: (i) their supposed safety because they exclude all risks of reversion of attenuated pathogens to a virulent form, (ii) their high specificity limiting the risk of autoimmune diseases, and (iii) the ease to produce, conserve, and transport them
Summary
Live attenuated vaccines (LAVs), composed of live pathogens that are made much less virulent than the pathogenic parental strains, are one of the most cost effective health tools in medical history [for review see [1,2,3]]. The advantages of LAVs include their mimicry of natural infections, the stimulation of long-term humoral and cellular immunity and their intrinsic adjuvant properties. First generation LAVs relied on empirical and somewhat unpredictable attenuation. In the present regulatory environment, the use of LAVs has been limited by safety concerns, especially due to the risk of reversion to wild-type virulence and the possibility of causing disease in immune compromised individuals. Advances in immunology, molecular virology and bacteriology have paved the way for the rational design of LAVs while avoiding the unpredictability of empirical attenuation to reduce the safety risks.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
